What is the likely diagnosis and treatment for a patient with low back pain, hip and thigh pain, joint pain, Raynaud's phenomenon, skin discoloration, and abnormal urinalysis results, including proteinuria and leukocyturia, with a history of hepatosplenomegaly and leukopenia?

Systemic Lupus Erythematosus with Lupus Nephritis

This clinical presentation is most consistent with systemic lupus erythematosus (SLE) with lupus nephritis, requiring urgent serologic testing, renal biopsy, and initiation of immunosuppressive therapy. 1

Diagnostic Rationale

The constellation of findings strongly suggests SLE with renal involvement:

• Musculoskeletal manifestations: Low back pain, hip/thigh pain, joint pain in fingers/hands, and thigh spasms indicate inflammatory arthritis/arthralgia typical of SLE 2
• Vascular phenomena: Raynaud's phenomenon, purple skin discoloration, slow capillary refill, and skin blanching suggest vasculopathy and microvascular dysfunction seen in connective tissue diseases 3, 4
• Hematologic abnormalities: Leukopenia is a common manifestation of SLE and represents one of the diagnostic criteria 2
• Hepatosplenomegaly: Suggests systemic inflammatory disease with reticuloendothelial involvement 2
• Renal involvement: The urinalysis showing proteinuria, leukocytes, bilirubin, urobilinogen, and multiple casts (waxy, granular, hyaline) indicates glomerulonephritis with tubular dysfunction 1

The presence of proteinuria with cellular casts strongly suggests glomerular disease, and the systemic features point toward lupus nephritis rather than isolated kidney disease. 1

Immediate Diagnostic Workup

Serologic testing must be obtained urgently:

• Antinuclear antibody (ANA) and anti-double stranded DNA antibodies to confirm SLE 1
• Complement levels (C3, C4, CH50) to identify hypocomplementemic glomerulopathy, which is characteristic of active lupus nephritis 1
• Complete metabolic panel including serum creatinine, BUN, electrolytes, and albumin to assess renal function and degree of hypoalbuminemia 1
• 24-hour urine protein quantification or spot urine protein-to-creatinine ratio to quantify proteinuria 1
• ANCA testing (anti-MPO and anti-PR3) to exclude vasculitis as an alternative diagnosis 1

Renal biopsy is mandatory and should include tissue for light microscopy, immunofluorescence, and electron microscopy to determine the ISN/RPS class of lupus nephritis and guide treatment. 1 Given the presence of proteinuria with abnormal urinalysis, biopsy should not be delayed even if proteinuria is <0.5 g/day, as significant histologic disease can be present at lower levels of proteinuria. 2

Treatment Approach

Initiate treatment based on biopsy results:

• Blood pressure control targeting <130/80 mmHg using ACE inhibitors or ARBs as first-line therapy 1
• For proliferative lupus nephritis (Class III or IV): Corticosteroids combined with either cyclophosphamide or mycophenolate mofetil per American College of Rheumatology guidelines 1
• Hydroxychloroquine should be started at a dose up to 5 mg/kg/day (maximum 400 mg/day) as it reduces flares and improves kidney outcomes in SLE 2

The combination of systemic manifestations with renal involvement requires aggressive immunosuppression to prevent progression to chronic kidney disease or kidney failure. 2

Monitoring Strategy

Serial monitoring is essential:

• Repeat urinalysis and proteinuria quantification every 3-6 months after treatment initiation, with a goal of reducing proteinuria to <0.5-1 g/day 1
• Serial complement levels to monitor disease activity in hypocomplementemic glomerulopathy 1
• Serum creatinine and eGFR monitoring to assess treatment response and disease progression 1
• Annual retinal examinations after 1 year of hydroxychloroquine therapy in high-risk patients or after 5 years in low-risk patients 2

Critical Pitfalls to Avoid

Do not delay renal biopsy waiting for serologic results, as histologic classification is essential for treatment decisions and biopsy can be performed safely even with active disease. 1

Do not dismiss low-level proteinuria as insignificant—92% of patients with <1 g/g proteinuria can have significant ISN/RPS class III, IV, V, or mixed histology on biopsy. 2

Raynaud's phenomenon in this context is secondary to connective tissue disease rather than primary Raynaud's disease, given the presence of systemic features and abnormal laboratory findings. 3, 4 Only 5% of primary Raynaud's patients develop connective tissue disease over a decade, but when systemic features are present at onset, secondary causes must be aggressively pursued. 5

Monitor for infection risk with immunosuppression, particularly Pneumocystis jirovecii prophylaxis in patients receiving prednisone ≥20 mg/day for >1 month combined with cyclophosphamide. 2